tbuckley/cabot-search huggingface dataset:
Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies: the CoPPS Statement
Authors: David Hohenschurz-Schmidt, Lene Vase, Whitney Scott, Marco Annoni, Oluwafemi K Ajayi, Jürgen Barth, Kim Bennell, Chantal Berna, Joel Bialosky, Felicity Braithwaite, Nanna B Finnerup, Amanda C de C Williams, Elisa Carlino, Francesco Cerritelli, Aleksander Chaibi, Dan Cherkin, Luana Colloca, Pierre Côté, Beth D Darnall, Roni Evans, Laurent Fabre, Vanda Faria, Simon French, Heike Gerger, Winfried Häuser, Rana S Hinman, Dien Ho, Thomas Janssens, Karin Jensen, Chris Johnston, Sigrid Juhl Lunde, Francis Keefe, Robert D Kerns, Helen Koechlin, Alice Kongsted, Lori A Michener, Daniel E Moerman, Frauke Musial, David Newell, Michael Nicholas, Tonya M Palermo, Sara Palermo, Kaya J Peerdeman, Esther M Pogatzki-Zahn, Aaron A Puhl, Lisa Roberts, Giacomo Rossettini, Susan Tomczak Matthiesen, Martin Underwood, Paul Vaucher, Jan Vollert, Karolina Wartolowska, Katja Weimer, Christoph Patrick Werner, Andrew S C Rice, Jerry Draper-Rodi
Journal: BMJ (2023)

Control interventions (often called "sham," "placebo," or "attention controls") are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers' decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour.
Ann Robinson’s research reviews—25 May 2023
Authors: Ann Robinson
Journal: BMJ (2023)

Waking up to diversityWe've woken up to the fact that research that focuses on richer countries alone is of limited value.Most of what we know about the epidemiology of common conditions such as heart failure comes from high income countries rather than low and middle income countries.This study of over 23 000 patients with heart failure from 40 low to high income countries found that the percentage of patients receiving optimal treatment was lower (45.7% v 61.9%), standardised mortality rates were higher (19.1 v 7.8/100 person-years), and the risk of dying within a month of first hospital admission was 3-5 times higher in low income compared with high income countries.There were substantial differences in causes, management, and outcomes in heart failure which need to be understood for planning and implementation.Any doctor working in a diverse city such as London will know that narrowly focused research is useless.
Correction: Evaluation of bleeding events in patients receiving acalabrutinib therapy
Authors: Pooja S. Kumar, Tracy Wiczer, Lindsay Rosen, Arthur J. Pollauf, Amy Zheng, Marilly Palettas, Leylah Azali, Seema A. Bhat, John C. Byrd, Michael R. Grever, Kerry A. Rogers, Jennifer A. Woyach, Adam S. Kittai
Journal: Leukemia (2023)
Urban and Rural Mpox Incidence Among Persons Aged 15–64 Years — United States, May 10–December 31, 2022
Authors: Carla E. Zelaya, Brandi P. Smith, Aspen P. Riser, Jaeyoung Hong, Samantha Distler, Siobhán O’Connor, Ermias Belay, Mohammad Shoeb, Michelle A. Waltenburg, Maria E. Negron, Sascha Ellington
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

During May 10-December 31, 2022, a total of 29,980 confirmed and probable† U.S. monkeypox (mpox) cases were reported to CDC, predominantly in cisgender adult men reporting recent same-gender sexual partners (1). Urban-rural differences in health (2) and diagnosis of HIV (3,4) and other sexually transmitted infections (5) are well documented nationally. This report describes urban-rural differences in mpox incidence (cases per 100,000 population) among persons aged 15-64 years, by gender and race and ethnicity. Urbanicity was assessed using the 2013 National Center for Health Statistics (NCHS) Urban-Rural Classification Scheme for Counties (2). Substantial differences in incidence by urbanicity, gender, and race and ethnicity were observed; most (71.0%) cases occurred in persons residing in large central urban areas. Among the cases in large central urban areas, most (95.7%) were in cisgender men. The overall incidence of mpox in the United States was 13.5 per 100,000 persons aged 15-64 years and peaked in August in both urban and rural areas. Among cisgender men, incidence in rural areas was approximately 4% that in large central urban areas (risk ratio [RR] = 0.04). Among cisgender women, incidence in rural areas was approximately 11% that in large central urban areas (RR = 0.11). In both urban and rural areas, incidence among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) persons was consistently higher than that among non-Hispanic White (White) persons; RRs between Black and White persons were highest in rural areas. Support and maintenance of mpox surveillance and prevention efforts including vaccinations should focus on urban areas with the highest incidence of mpox during the 2022 outbreak; however, surveillance and prevention efforts should include all genders, persons of color, and persons residing in both urban and rural areas who are at increased risk for mpox.
Fine-tuning germline mutation rates across evolution
Authors: Stephen J. Bush, Anne Goriely
Journal: Trends in Genetics (2023)

The germline mutation rate (GMR) sets the pace at which mutations, the raw material of evolution, are introduced into the genome. By sequencing a dataset of unprecedently broad phylogenetic scope, Bergeron et al. estimated species-specific GMR, offering numerous insights into how this parameter shapes and is shaped by life-history traits.
The relationship between gastro-oesophageal reflux and pulmonary fibrosis: a never-ending story
Authors: Maria Molina-Molina
Journal: European Respiratory Journal (2023)

<b>Higher risk of IPF in the presence of a genetic predisposition to GORD increases the evidence for this causal relationship. Many other factors are involved in this complex story, which will be understood through the integration of different variables.</b>https://bit.ly/3LbiPga
“Nintedanib in children and adolescents with fibrosing interstitial lung diseases.” R. Deterding, L.R. Young, E.M. DeBoer, D. Warburton, S. Cunningham, N. Schwerk, K.R. Flaherty, K.K. Brown, M. Dumistracel, E. Erhardt, J. Bertulis, M. Gahlemann, S. Stowasser and M. Griese for the InPedILD trial investigators.<i>Eur Respir J</i>2023; 61: 2201512
Journal: European Respiratory Journal (2023)

Due to a programming error, one patient in the age 12-17 year group was omitted from the analyses presented in this study.This resulted in incorrect data being included in supplementary table S4.Table S4 in the supplementary materials has been amended to correct this.Furthermore, the following sentence in the Pharmacokinetics section of the Results, has been changed from:"The geometric mean (gCV) AUCτ,ss for nintedanib was 175 µg•h•L -1 (85.1%) in patients aged 6-11 years and 160 µg•h•L -1 (82.7%) in patients aged 12-17 years."to:"The geometric mean (gCV) AUCτ,ss for nintedanib was 175 µg•h•L -1 (85.1%) in patients aged 6-11 years and 167 µg•h•L -1 (83.6%) in patients aged 12-17 years.
Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B
Authors: Na Sang, Xi Zhong, Kun Gou, Huan Liu, Jing Xu, Yang Zhou, Xia Zhou, Yuanzhi Liu, Zhiqian Chen, Yue Zhou, Yan Li, Lei Tao, Na Su, Lingyun Zhou, Jiahao Qiu, Xinyu Yang, Zeping Zuo, Li Fu, Jingyao Zhang, Dan Li, Cong Li, Qingxiang Sun, Jian Lei, Rui Li, Shengyong Yang, Xiaobo Cen, Yinglan Zhao
Journal: MedComm (2023)

Lysine-specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell-derived and patient-derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage-inducible gene 45beta (
Effectiveness of chatbots on COVID vaccine confidence and acceptance in Thailand, Hong Kong, and Singapore
Authors: Kristi Yoonsup Lee, Saudamini Vishwanath Dabak, Vivian Hanxiao Kong, Minah Park, Shirley L. L. Kwok, Madison Silzle, Chayapat Rachatan, Alex Cook, Aly Passanante, Ed Pertwee, Zhengdong Wu, Javier A. Elkin, Heidi J. Larson, Eric H. Y. Lau, Kathy Leung, Joseph T. Wu, Leesa Lin
Journal: npj Digital Medicine (2023)

Chatbots have become an increasingly popular tool in the field of health services and communications. Despite chatbots' significance amid the COVID-19 pandemic, few studies have performed a rigorous evaluation of the effectiveness of chatbots in improving vaccine confidence and acceptance. In Thailand, Hong Kong, and Singapore, from February 11th to June 30th, 2022, we conducted multisite randomised controlled trials (RCT) on 2,045 adult guardians of children and seniors who were unvaccinated or had delayed vaccinations. After a week of using COVID-19 vaccine chatbots, the differences in vaccine confidence and acceptance were compared between the intervention and control groups. Compared to non-users, fewer chatbot users reported decreased confidence in vaccine effectiveness in the Thailand child group [Intervention: 4.3 % vs. Control: 17%, P = 0.023]. However, more chatbot users reported decreased vaccine acceptance [26% vs. 12%, P = 0.028] in Hong Kong child group and decreased vaccine confidence in safety [29% vs. 10%, P = 0.041] in Singapore child group. There was no statistically significant change in vaccine confidence or acceptance in the Hong Kong senior group. Employing the RE-AIM framework, process evaluation indicated strong acceptance and implementation support for vaccine chatbots from stakeholders, with high levels of sustainability and scalability. This multisite, parallel RCT study on vaccine chatbots found mixed success in improving vaccine confidence and acceptance among unvaccinated Asian subpopulations. Further studies that link chatbot usage and real-world vaccine uptake are needed to augment evidence for employing vaccine chatbots to advance vaccine confidence and acceptance.
Systematic characterization of regulatory variants of blood pressure genes
Authors: Winona Oliveros, Kate Delfosse, Daniella F. Lato, Katerina Kiriakopulos, Milad Mokhtaridoost, Abdelrahman Said, Brandon J. McMurray, Jared W.L. Browning, Kaia Mattioli, Guoliang Meng, James Ellis, Seema Mital, Marta Melé, Philipp G. Maass
Journal: Cell Genomics (2023)

High blood pressure (BP) is the major risk factor for cardiovascular disease. Genome-wide association studies have identified genetic variants for BP, but functional insights into causality and related molecular mechanisms lag behind. We functionally characterize 4,608 genetic variants in linkage with 135 BP loci in vascular smooth muscle cells and cardiomyocytes by massively parallel reporter assays. High densities of regulatory variants at BP loci (i.e., ULK4, MAP4, CFDP1, PDE5A) indicate that multiple variants drive genetic association. Regulatory variants are enriched in repeats, alter cardiovascular-related transcription factor motifs, and spatially converge with genes controlling specific cardiovascular pathways. Using heuristic scoring, we define likely causal variants, and CRISPR prime editing finally determines causal variants for KCNK9, SFXN2, and PCGF6, which are candidates for developing high BP. Our systems-level approach provides a catalog of functionally relevant variants and their genomic architecture in two trait-relevant cell lines for a better understanding of BP gene regulation.
Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
Authors: Elena Martín-González, José M. Hernández-Pérez, José A. Pérez Pérez, Javier Pérez-García, Esther Herrera-Luis, Ruperto González-Pérez, Orelvis González-González, Elena Mederos-Luis, Inmaculada Sánchez-Machín, Paloma Poza-Guedes, Olaia Sardón, Paula Corcuera, María J. Cruz, Francisco J. González-Barcala, Carlos Martínez-Rivera, Joaquim Mullol, Xavier Muñoz, José M. Olaguibel, Vicente Plaza, Santiago Quirce, Antonio Valero, Joaquín Sastre, Javier Korta-Murua, Victoria del Pozo, Fabián Lorenzo-Díaz, Jesús Villar, María Pino-Yanes, Mario A. González-Carracedo
Journal: Pulmonology (2023)

Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations.In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates.In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55-7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007).AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.
Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity
Authors: Benjamin J. Jenkins, Julianna Blagih, Fernando M. Ponce-Garcia, Mary Canavan, Nancy Gudgeon, Simon Eastham, David Hill, Megan M. Hanlon, Eric H. Ma, Emma L. Bishop, April Rees, James G. Cronin, Elizabeth C. Jury, Sarah K. Dimeloe, Douglas J. Veale, Catherine A. Thornton, Karen H. Vousden, David K. Finlay, Ursula Fearon, Gareth W. Jones, Linda V. Sinclair, Emma E. Vincent, Nicholas Jones
Journal: Cell Metabolism (2023)

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity.
Abstract 1382: Effects of Recreational Dance Exercise on Vascular Structure and Function in Older Women
Authors: Sae Young Jae, Soo Jin Jung, Eun Sun Yoon, Sung Kun Chun, Tae Yeol Son, Kevin Heffernan, Bo Fernhall
Journal: Circulation (2009)

Objective. Aging has a negative effect on large elastic artery structure and function which increases the risk of cardiovascular disease (CVD). Although a number of studies suggest that exercise is...
Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes
Authors: Huabing Zhang, Jorge Plutzky, Maria Shubina, Alexander Turchin
Journal: Annals of Internal Medicine (2017)

Background: Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. Objective: To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Design: Retrospective cohort study. Setting: Primary care practices affiliated with 2 academic medical centers. Participants: Patients with a presumed adverse reaction to a statin between 2000 and 2011. Measurements: Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Results: Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. Limitations: The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Conclusion: Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Primary Funding Source: Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.
1. Improving Care and Promoting Health in Populations: <i>Standards of Medical Care in Diabetes—2018</i>
Journal: Diabetes Care (2017)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multi-disciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/content/clinical-practice-recommendations.
GATA3 mediates doxorubicin resistance by inhibiting CYB5R2-catalyzed iron reduction in breast cancer cells
Authors: Zhen Zhu, Hongyu Shen, Jialin Xu, Zheng Fang, Guanqun Wo, Ying Ma, Kai Yang, Yalin Wang, Qiang Yu, Jin-hai Tang
Journal: Drug Resistance Updates (2023)

Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.